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Pharmacokinetics of Pediatric Lopinavir/Ritonavir Tablets in Children When Administered Twice Daily According to FDA Weight Bands

Bastiaans, Diane E. T. PharmD*; Forcat, Silvia PharmD, PhD; Lyall, Hermione MB ChB(Hons), MD, FRCPCH; Cressey, Tim R. PhD§; Hansudewechakul, Rawiwan MD; Kanjanavanit, Suparat MD; Noguera-Julian, Antoni MD, PhD**; Königs, Christoph MD††; Inshaw, Jamie R. J. MSc; Chalermpantmetagul, Suwalai RN, MSc§; Saïdi, Yacine PhD‡‡; Compagnucci, Alexandra MD‡‡; Harper, Lynda M. MSc; Giaquinto, Carlo MD§§; Colbers, Angela P. H. MSc*; Burger, David M. PharmD, PhD*on Behalf of PENTA 18KONCERT Study Group

The Pediatric Infectious Disease Journal: March 2014 - Volume 33 - Issue 3 - p 301–305
doi: 10.1097/INF.0000000000000014
HIV Reports

Background: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose. In addition, weight band–based dosing has not been formally studied in the target population. We evaluated the pharmacokinetics (PK) of LPV/r in children, administered twice daily according to the FDA weight bands, using pediatric tablets.

Methods: Fifty-three HIV-infected children were included in the PK substudy of the Paediatric European Network for the Treatment of AIDS 18 trial (KONCERT). In this study, children were randomized to receive LPV/r twice or once daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and 20 children in the 15–25 kg, ≥25–35 kg and >35 kg weight band, respectively, while children took the tablets twice daily. Rich sampling was performed, and PK parameters were calculated by noncompartmental analysis. Given the high percentage of Asian children, it was also tested whether there was a difference in PK parameters between Asian and non-Asian children.

Results: For the total group, LPV geometric mean AUC0–12, Cmax and C12 were 106.9 h × mg/L, 12.0 mg/L and 4.9 mg/L, respectively. There were no significant differences in LPV PK parameters between the weight bands. In addition, weight was not found to be associated with variability in Cmax, C12 or AUC0–12 for the LPV PK parameters.

Conclusions: FDA weight band–based dosing recommendations provide adequate exposure to LPV when using LPV/r pediatric tablets.

Supplemental Digital Content is available in the text.

From the *Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; MRC, Clinical Trials Unit, London, United Kingdom; Imperial College Healthcare NHS Trust, Department of Pediatrics, St Mary’s Hospital, London, United Kingdom; §Program for HIV Prevention and Treatment/IRD UMI-174, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Department of Pediatrics, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; Department of Pediatrics, Nakornping Hospital, Chiang Mai, Thailand; **Unitat d´Infectologia, Servei de Pediatria, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; ††Department of Pediatrics and Adolescent Medicine, J.W. Goethe University, Frankfurt, Germany; ‡‡INSERM, SC10-US19, Villejuif, France; and §§Department of Pediatrics, University of Padova, Italy.

Accepted for publication July 19, 2013.

Paediatric European Network for Treatment of AIDS (PENTA)—funding from the European Union Seventh Framework Program (FP7/2007–2013) under EuroCoord grant agreement no 260694 with financial support for this trial from Abbott Laboratories. Abbott Pharmaceuticals supplied LPV/r tablets to sites in Germany, Spain, France and Thailand. Trial participants in other countries were provided LPV/r from commercial stock. C.G. received travel/accommodations/meeting expenses from ViiV/GSK. The authors have no other conflicts of interest to disclose.

Collaborators’ list are given in Appendix, Supplemental Digital Content 3, http://links.lww.com/INF/B691.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Diane E. T. Bastiaans, PharmD, Department of Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: d.bastiaans@akf.umcn.nl.

© 2014 by Lippincott Williams & Wilkins, Inc.